Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis

Becker, Jill B.; Perry, Adam N.; Westenbroek, Christel

doi:10.1186/2042-6410-3-14

Cited by 267 publications

(263 citation statements)

References 516 publications

(508 reference statements)

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“…Nevertheless, more men than women initiate illicit drug use (55.1% vs. 44%; and for cocaine, 18.1% vs. 11.4%), which may account for the higher rate overall of drug abuse among men (3.6% vs. 2.0%; SAMHSA 2010). These findings suggest a differential path to abuse for men and women (for review, see Becker et al 2012) or, alternatively, reflect the greater propensity for women to remain abstinent following treatment for drug abuse (Weiss et al 1997). Our finding that E 2 treatment enhanced extinction of cocaine seeking even in ovariectomized rats that were perseverating for up to 5 wk suggests a potentially vital role for E 2 in the recovery from cocaine abuse.…”

Section: Discussionmentioning

confidence: 73%

“…Estrogens are key hormones that regulate the response to cocaine in both female rats and humans (Segarra et al 2010). Changes in estrogen levels in cycling females may account for the apparent greater severity of cocaine addiction, or faster transition from use to abuse, relative to that of men (Becker et al 2012). Nevertheless, more men than women initiate illicit drug use (55.1% vs. 44%; and for cocaine, 18.1% vs. 11.4%), which may account for the higher rate overall of drug abuse among men (3.6% vs. 2.0%; SAMHSA 2010).…”

Section: Discussionmentioning

confidence: 99%

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17β-Estradiol is necessary for extinction of cocaine seeking in female rats

et al. 2013

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Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17b-estradiol (E 2 ) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E 2 treatment followed by 2 d of vehicle treatment, or were injected with E 2 daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E 2 levels during conditioning did not affect subsequent CPP expression. During extinction, daily E 2 administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E 2 -treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E 2 could rescue extinction in these rats, half were given daily E 2 treatment and half were given vehicle. E 2 -treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E 2 is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E 2 levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts.Gonadal hormones render women more susceptible than men to developing compulsive patterns of psychostimulant use. Natural fluctuations in levels of the primary ovarian hormones, estrogens and progesterone, account for this increased abuse liability. Higher levels of estrogens, and lower levels of progesterone, are associated with greater sensitivity to the euphorigenic properties of cocaine in women (Evans 2007). This increased sensitivity may contribute to why women, compared with men, start using cocaine regularly at a younger age (Chen and Kandel 2002), transition from use to abuse more quickly (McCance-Katz et al. 1999), experience greater craving in response to drug-associated cues (Robbins et al. 1999) and stress (Potenza et al. 2012;Waldrop et al. 2012), and exhibit more severe drug-seeking behavior upon relapse (Gallop et al. 2007). In contrast, more women than men remain abstinent after treatment (Weiss et al. 1997). Thus, women are both more susceptible to cocaine abuse and, paradoxically, more responsive to treatment.A substantial literature supports that estrogens mediate the enhancement of drug seeking observed in females (Febo et al. 2002;Larson et al. 2007;Segarra et al. 2010; Kerstetter and Kippin 2011), but little is known regarding the role of estrogens during treatment. Preclinically, treatment is modeled through ext...

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

et al. 2013

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“…The latter may be skewed by social factors such as willingness to seek treatment. Likewise, varying rates of drug and alcohol abuse in men and women are speculated to be based in sex differences in risk-seeking and reward systems, as opposed to a neural substrate of addiction that is sexually dimorphic [89].…”

Section: Sex Differences In Diseases and Disorders Of The Nervous Systemmentioning

confidence: 99%

Multifaceted origins of sex differences in the brain

McCarthy

2016

Phil. Trans. R. Soc. B

150

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Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.

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“…Ces sujets vont ajouter à leurs symptômes négatifs les effets de la dépendance à la drogue. Pour faire face à cette double charge négative, ils devront augmenter la quantité et la fréquence de leur consommation de drogue et ils se retrouveront ainsi plus rapidement dans l'abîme de la dépendance, tout en ayant plus de difficultés à mettre fin à leur accoutumance (Becker et al, 2012). Il semble que la proportion d'individus qui deviennent dépendants à l'usage des drogues illicites par l'une ou l'autre de ces voies est diffé-rente chez les hommes et les femmes (Becker et Hu, 2008 ;Caroll et al, 2004).…”

Section: Motivation Initialeunclassified

“…Récemment, même si le problème demeure toujours largement l'apanage des hommes, l'écart qui les sépare des femmes a rétréci de façon importante. De plus, les femmes semblent plus susceptibles de développer une dépen-dance aux drogues, souffrent plus sévèrement des conséquences physiologiques et psychologiques de la consommation de drogues, et éprouvent plus de difficultés à briser leur dépendance (Becker et Hu, 2008 ;Becker et al, 2012 ;Caroll et al, 2004). Les raisons qui expliquent ces différences entre les hommes et les femmes sont multiples et complexes.…”

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Existe-t-il des différences entre les hommes et les femmes en ce qui concerne les problèmes de toxicomanie ?

Mendrek

2014

smq

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La consommation et la dépendance aux drogues furent longtemps considérées comme un problème typiquement masculin. Néanmoins, bien que l’abus et la dépendance à l’alcool, au cannabis et à la nicotine soient encore plus répandus chez les hommes, les différences de genre en ce qui concerne les stimulants et les opiacés ont largement disparu. Il semblerait également que les motivations pour commencer à consommer, l’escalade vers la dépendance et les taux de cessation diffèrent chez les hommes et les femmes. Les raisons qui expliquent ces différences sont multiples et complexes. Nous allons examiner ici les données des études épidémiologiques et cliniques concernant la consommation de diverses drogues chez des hommes et chez des femmes en contexte des facteurs socioculturels, psychologiques et neurobiologiques.Drug use and drug addiction have been traditionally considered to be a male problem, however the gender gap has been decreasing over the past few decades. Thus, while the prevalence of alcohol, cannabis and nicotine dependence is still overall greater among men than among women, sex/gender differences in the abuse of stimulants and opiates seem to have disappeared. Moreover, women appear to be more prone to develop drug dependence, suffer more severe physical and psychological consequences of drug abuse, and have more difficulties quitting the habit. Numerous psychological, socio-cultural and biological factors have been implicated in these changing statistics. For example, while a large proportion of men initiate drug use to induce feelings of elation, energy or focus, women frequently start taking drugs to alleviate pre-existing mental health problems, including high levels of stress, feelings of alienation, depression, anxiety, or post-traumatic stress disorder. This maladaptive self-medication strategy often results in a faster transition to a habitual drug use and eventually a more severe dependence. In addition, the socio-cultural norms (particularly in the Western society) have changed dramatically over the past few decades. Thus, while there is still a more severe stigma and prejudice against women who use drugs (especially if they are pregnant of have children), overall there is much greater acceptance of women’s drug use than it was several decades ago. Moreover, women have much greater access to various drugs of abuse than they used to have. Finally, over the past couple of decades new research started emerging pointing to some neurobiological factors that could also contribute to sex differences in drug addiction. Thus, there is now evidence that dopamine system, which for decades has been strongly implicated in drug reinforcement, is sexually dimorphic. The number of dopaminergic neurons, the density of the dopaminergic terminals, as well as responsiveness of the dopaminergic system to drugs of abuse, has been shown to differ between males and females and it has been shown to be modulated by sex steroid hormones, especially estrogen. For example, female rats exhibit greater motivation to self-admini...

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Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis

Cited by 267 publications

References 516 publications

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

Multifaceted origins of sex differences in the brain

Existe-t-il des différences entre les hommes et les femmes en ce qui concerne les problèmes de toxicomanie ?

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